(PS3-44) Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder: A Proof-of-concept Trial

Introduction: Recent advances in understanding the pathophysiology of Major Depressive Disorder (MDD) have focused on the dysregulation of glutamate and associated neuronal glutaminergic excitotoxicity. Ketamine is an NMDA receptor antagonist that has demonstrated effective modulation of glutamate transmission resulting in rapid antidepressant effects and has shown to be well tolerated in both MDD and bipolar depression. However, ketamine has been shown to have limitations in the clinical world. One is the side effect of dissociation and the potential for visual or auditory hallucinations. Xenon is a potent anti-glutamatergic anesthetic agent with effects similar to ketamine with minimal side effects while demonstrating neuroprotective effects consistent with antidepressants. This study is the first to assess the potential of repurposed inhaled Xenon as a novel antidepressant drug.  

Methods: We aim to recruit 20 severely depressed patients between the ages of 18-65, 10 with major depressive disorder (MDD) and 10 with Bipolar Disorder (BD). Thus far, seven MDD participants and two BD participants have fully completed all study tasks. Participants have been recruited primarily through MGH’s Rally platform, Research Patient Data Repository, Patient Gateway, and from the waiting list of the MGH Ketamine Clinic. Participants undergo a screening phone call and an in-person screening visit to confirm eligibility. Each participant completes two double-blind treatment visits (either xenon or room air), that are randomized beforehand to determine the order of their administration. Steady xenon concentrations are delivered and monitored using an FDA approved device. Post-administration, participants complete follow-up assessments to evaluate depressive, manic, and anxiety symptoms as well as therapeutic efficacy and possible study-related side effects at 40, 80, 110, and 230 minutes after treatment. Participants are additionally followed up via phone call for 1,2,3, and 7 days after treatment. Our primary outcome is improvement of depressive symptoms on day 1 according to a blind rating of the modified Hamilton Depression Rating Scale at baseline and the above predefined time intervals. We hypothesize a greater decrease in depressive symptoms after one session of xenon inhalation compared to their session with nitrogen-oxygen.  


Discussion: We are assessing the acute efficacy of Xenon as a potential new antidepressant agent. The hypothesis is that Xenon will be well tolerated in unipolar and bipolar depression and alleviate depressive symptoms. 45% of desired participants have fully completed the study and 67% of that group labeled themselves as White. The goal is to recruit from more diverse populations as the study continues.